Mesenchymal stem cells (MSCs) are multipotent stem cells capable of differentiating into adipocytes in the presence of a hormone cocktail. These cells thus provide a promising model for studying the early events of adipogenesis. Here, we examine the involvement of the PI3K/Akt and mTOR/p70S6K signaling pathways in human MSC adipogenesis. We found that the two pathways were strongly activated with a similar temporal profile under the adipogenesis-inducing hormone cocktail and this activation could be blocked by LY294002, a specific inhibitor of PI3K. Furthermore, rapamycin, a specific inhibitor of mTOR, blocked the activation of mTOR/p70S6K but not PI3K/Akt. Both LY294002 and rapamycin severely suppressed lipid accumulation, as well as the expression of adipogenic markers, including PPAR gamma 2 and C/EBP alpha, two master adipogenic transcription factors. Together, these data indicate that the mTOR/p70S6K pathway acts downstream of the PI3K/Akt pathway in mediating the adipogenic conversion of MSCs. In conclusion, our data suggest that the PI3K/Akt and mTOR/p70S6K signaling pathways are essential for adipogenesis of human MSCs.

Estrogen receptor (ER) and insulin‐like growth factor‐1 receptor (IGF‐1R) signaling are implicated in lung cancer progression. Based on their previous findings, the authors sought to investigate whether estrogen and IGF‐1 act synergistically to promote lung adenocarcinoma (LADE) development in mice. LADE was induced with urethane in ovariectomized Kunming mice. Tumor‐bearing mice were divided into seven groups: 17β‐estradiol (E2), E2+fulvestrant (Ful; estrogen inhibitor), IGF‐1, IGF‐1+AG1024 (IGF‐1 inhibitor), E2+IGF‐1, E2+IGF‐1+Ful+AG1024 and control groups. After 14 weeks, the mice were sacrificed, and then the tumor growth was determined. The expression of ERα/ERβ, IGF‐1, IGF‐1R and Ki67 was examined using tissue‐microarray‐immunohistochemistry, and IGF‐1, p‐ERβ, p‐IGF‐1R, p‐MAPK and p‐AKT levels were determined based on Western blot analysis. Fluorescence‐quantitative polymerase chain reaction was used to detect the mRNA expression of ERβ, ERβ2 and IGF‐1R. Tumors were found in 93.88% (46/49) of urethane‐treated mice, and pathologically proven LADE was noted in 75.51% (37/49). In the E2+IGF‐1 group, tumor growth was significantly higher than in the E2 group (p < 0.05), the IGF‐1 group (p < 0.05) and control group (p < 0.05). Similarly, the expression of ERβ, p‐ERβ, ERβ2, IGF‐1, IGF‐1R, p‐IGF‐1R, p‐MAPK, p‐AKT and Ki67 at the protein and/or mRNA levels was markedly higher in the ligand group than in the ligand + inhibitor groups (all p < 0.05). This study demonstrated for the first time that estrogen and IGF‐1 act to synergistically promote the development of LADE in mice, and this may be related to the activation of the MAPK and AKT signaling pathways in which ERβ1, ERβ2 and IGF‐1R play important roles.

The regulatory T cells (Treg) play an important role in the tumor tolerance. The methods to regulate the Treg population in cancer-bearing hosts are limited currently. The effect of curcumin on inhibiting cancer has been recognized, but the mechanism remains elusive. This study tests a hypothesis that administration of curcumin down regulates Tregs in lung cancer (LC) patients. In this study, a group of LC patients was treated with curcumin. The peripheral Tregs and T helper (Th) 1 cells were analyzed by flow cytometry. The mechanism by which curcumin regulated the Tregs was observed by cell culture approaches. The results showed that the frequency of peripheral Treg was markedly higher in LC patients than that in healthy subjects, which was suppressed after treating with curcumin for 2 weeks. The peripheral Th1 cells were increased in LC patients after the curcumin therapy. The data of the in vitro experiments showed that curcumin converted the LC patient-isolated Tregs to Th1 cells via repressing the gene transcription of forkhead protein-3 and increasing the expression of interferon-γ. In conclusion, curcumin can convert LC patient-isolated Tregs to Th1 cells. The results suggest that curcumin may improve the antitumor immunity by regulating the tumor specific immune tolerance.

Background Expression of the stem cell marker octamer 4 (Oct-4) in various neoplasms has been previously reported, but very little is currently known about the potential function of Oct-4 in this setting. The purpose of this study was to assess the prognostic value of Oct-4 expression after surgery in primary non-small cell lung cancer (NSCLC) and investigate its possible molecular mechanism. Methods We measured Oct-4 expression in 113 NSCLC tissue samples and three cell lines by immunohistochemical staining and RT-PCR. The association of Oct-4 expression with demographic characteristics, proliferative marker Ki67, microvessel density (MVD), and expression of vascular endothelial growth factor (VEGF) were assessed. Results Oct-4 expression was detected in 90.3% of samples and was positively correlated with poor differentiation and adenocarcinoma histology, and Oct-4 mRNA was found in each cell lines detected. Overexpression of Oct-4 had a strong association with cells proliferation in all cases, MVD-negative, and VEGF-negative subsets. A Kaplan-Meier analysis showed that overexpression of Oct-4 was associated with shorter overall survival in all cases, adenocarcinoma, squamous cell carcinoma, MVD-negative, and VEGF-negative subsets. A multivariate analysis demonstrated that Oct-4 level in tumor tissue was an independent prognostic factor for overall survival in all cases, MVD-negative, and VEGF-negative subsets. Conclusion Our findings suggest that, even in the context of vulnerable MVD status and VEGF expression, overexpression of Oct-4 in tumor tissue represents a prognostic factor in primary NSCLC patients. Oct-4 may maintain NSCLC cells in a poorly differentiated state through a mechanism that depends on promoting cell proliferation.

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